Dry Eye
Conditions
Keywords
Dry Eye, Tear Film Lipid Layer Dynamics, Tear Film Stability
Brief summary
Dry eye disease (DED) is pervasive with some reports estimating over 16 million adults diagnosed in the United States. Currently, artificial tears remain an integral part of managing dry eyes and are mainly used for symptomatic relief. Recent studies have shown there may be therapeutic benefits with regular use of lipid-based artificial tears to improve the structure of the tear film, which may improve tear film stability and provide relief of symptoms. In this study the investigators propose to compare effects on the tear lipid film and its dynamics between 3 lipid based artificial tears and a widely available non-lipid based artificial tear.
Detailed description
This is a prospective, double-masked, randomized, controlled, parallel-group trial designed to compare the impact of Systane Complete PF lipid-based artificial tears (the Treatment solution under study) on tear lipid layer thickness compared with a non-lipid Control solution, Refresh Relieva PF. Secondarily, the study will compare changes in tear lipid layer thickness, lipid layer uniformity, tear film thinning dynamics, and symptoms between the Treatment solution, the non-lipid Control solution, and 2 other available lipid-based solutions (Active Comparators: Refresh Optive Mega-3 PF and CVS Health Lubricant Eye Drop (PG 0.6%)). The study will include 4 clinic visits, and require 1 week of single-masked run-in with Systane Ultra PF (an over-the-counter non-lipid-based solution) followed by 3 months of study treatment dosing. All subjects will complete a screening interview, then an in-clinic baseline ocular health examination and study eligibility determination followed by dispensing of the Control solution to all subjects for 1 week of run-in. After that week, subjects will be randomized to 1 of the 4 artificial tear solutions and have an in-clinic ocular examination and dispense of the assigned solution to use for 3 months. An in-clinic follow-up examination is completed after 1 month of study solution use, followed by a phone interview at 2 months, and a final in-clinic examination at 3 months post-dispensing.
Interventions
3 month use, 4 times daily, of Systane Complete PF, a lipid-based, preservative-free artificial tear product
DRUGRefresh Relieva PF
3 month use, 4 times daily, of Refresh Relieva PF, a non-lipid-based, preservative-free artificial tear product
DRUGRefresh Optive Mega-3 PF
3 month use, 4 times daily, of Refresh Optive Mega-3 PF, a lipid-based, preservative-free artificial tear product
DRUGCVS Health Lubricant Eye Drop (PG 0.6%)
3 month use, 4 times daily, of CVS Health Lubricant Eye Drop (PG 0.6%), a lipid-based, preserved artificial tear product
Sponsors
Alcon Research
University of California, Berkeley
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Masking description
After the 1-week initial period during which all subjects will use the run-in solution, subjects will be randomly assigned one of the 4 study solutions, and neither the subject nor the clinician researchers or technicians conducting examinations and taking measurements will be aware of which solution is assigned. All 4 solutions will be dispensed in color- and name-coded identical dispensing bottles prepared by study personnel not involved in collecting data.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Best Corrected Visual Acuity of 20/30 or better; * Experiencing Dry Eye symptoms (baseline OSDI score \>= 13);
Exclusion criteria
* Currently experiencing active ocular inflammation or infection; * Currently using topical eye medication (not including over-the-counter eyedrops); * Having systemic health conditions or using prescription medications (including but not limited to isotretinoin derivatives) that could alter tear film physiology; * Having a history of severe ocular trauma, ocular surgery, or diabetes; * Being pregnant or breast feeding; * Being a current contact lens wearer; * Currently having a condition or being in a situation which, in the examiner's opinion, may put the subject at significant risk, may confound the study results, or may otherwise significantly interfere with their participation in the study;
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Tear Lipid Layer Thickness | Lipid Layer Thickness measured once at post-run-in baseline and once at 3mo follow-up visit | Change in Tear Lipid Layer Thickness (3mo follow-up - post-run-in baseline) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Tear Lipid Layer Uniformity | Lipid Layer Uniformity measured once at post-run-in baseline and once at 3mo follow-up visit | Change (3mo follow-up - post-run-in baseline) in Tear Lipid Layer Thickness Coefficient of Variation (CV). The CV is calculated as the standard deviation divided by the mean lipid layer thickness. A greater value of the CV indicates more variability in lipid layer thickness, a smaller value of the CV indicates a more uniformly thick lipid layer. |
| Tear Film Thinning Rate | Tear Film Thinning Rate measured once at post-run-in baseline and once at 3mo follow-up visit | Change in Tear Film Thinning rate (3mo follow-up - post-run-in baseline) |
Other
| Measure | Time frame | Description |
|---|---|---|
| Exploratory - Subjective Symptoms - OSDI Questionnaire | OSDI questionnaire administered once at post-run-in baseline and once at 3mo follow-up visit | Change (3mo follow-up - post-run-in baseline) in Ocular Surface Disease Index (OSDI) score. The OSDI questionnaire score ranges from 0-100, with higher scores indicating more severe symptoms of Dry Eye Disease. |
| Exploratory - Subjective Symptoms - SANDE | SANDE questionnaire administered once at post-run-in baseline and once at 3mo follow-up visit | Change in Symptom Assessment questionnaire iN Dry Eye (SANDE) score (3mo follow-up - post-run-in baseline) |
| Exploratory - Subjective Symptoms - DEQ-5 | DEQ-5 questionnaire administered once at post-run-in baseline and once at 3mo follow-up visit | Change in 5-Item Dry Eye Questionnaire (DEQ-5) score (3mo follow-up - post-run-in baseline) |
Countries
United States
Participant flow
Pre-assignment details
All subjects participated in a 1-week run-in period during which they used a common over-the-counter non-lipid artificial tear (Systane Ultra PF). Upon completion of the run-in period, participants were then randomized to one of the 4 study solutions.
Participants by arm
| Arm | Count |
|---|---|
| Systane Complete PF (Treatment) Masked subjects assigned to Arm 1 will use Systane Complete PF artificial tear drops 4 times per day (QID) to treat dry eye symptoms over a 3 month period.
Systane Complete PF: 3 month use, 4 times daily, of Systane Complete PF, a lipid-based, preservative-free artificial tear product | 18 |
| Refresh Relieva PF (Control) Masked subjects assigned to Arm 2 will use Refresh Relieva PF artificial tear drops 4 times per day (QID) to treat dry eye symptoms over a 3 month period.
Refresh Relieva PF: 3 month use, 4 times daily, of Refresh Relieva PF, a non-lipid-based, preservative-free artificial tear product | 21 |
| Refresh Optive Mega-3 PF (Active Comparator 1) Masked subjects assigned to Arm 3 will use Refresh Optive Mega-3 PF artificial tear drops 4 times per day (QID) to treat dry eye symptoms over a 3 month period.
Refresh Optive Mega-3 PF: 3 month use, 4 times daily, of Refresh Optive Mega-3 PF, a lipid-based, preservative-free artificial tear product | 19 |
| CVS Health Lubricant Eye Drop (PG 0.6%) (Active Comparator 2) Masked subjects assigned to Arm 4 will use CVS Health Lubricant Eye Drop (PG 0.6%) artificial tear drops 4 times per day (QID) to treat dry eye symptoms over a 3 month period.
CVS Health Lubricant Eye Drop (PG 0.6%): 3 month use, 4 times daily, of CVS Health Lubricant Eye Drop (PG 0.6%), a lipid-based, preserved artificial tear product | 23 |
| Total | 81 |
Baseline characteristics
| Characteristic | Systane Complete PF (Treatment) | Refresh Relieva PF (Control) | Refresh Optive Mega-3 PF (Active Comparator 1) | CVS Health Lubricant Eye Drop (PG 0.6%) (Active Comparator 2) | Total |
|---|---|---|---|---|---|
| Age, Continuous | 36.3 years STANDARD_DEVIATION 16.1 | 34.0 years STANDARD_DEVIATION 16.6 | 38.4 years STANDARD_DEVIATION 17.1 | 35.5 years STANDARD_DEVIATION 17.3 | 36.0 years STANDARD_DEVIATION 16.6 |
| Race/Ethnicity, Customized Race/Ethnicity Group Asian | 10 Participants | 11 Participants | 3 Participants | 11 Participants | 35 Participants |
| Race/Ethnicity, Customized Race/Ethnicity Group Non-Asian | 8 Participants | 10 Participants | 16 Participants | 12 Participants | 46 Participants |
| Sex: Female, Male Female | 11 Participants | 16 Participants | 16 Participants | 16 Participants | 59 Participants |
| Sex: Female, Male Male | 7 Participants | 5 Participants | 3 Participants | 7 Participants | 22 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 81 | 0 / 18 | 0 / 21 | 0 / 19 | 0 / 23 |
| other Total, other adverse events | 0 / 81 | 0 / 18 | 0 / 21 | 0 / 19 | 0 / 23 |
| serious Total, serious adverse events | 0 / 81 | 0 / 18 | 0 / 21 | 0 / 19 | 0 / 23 |
Outcome results
Primary
Tear Lipid Layer Thickness
Change in Tear Lipid Layer Thickness (3mo follow-up - post-run-in baseline)
Time frame: Lipid Layer Thickness measured once at post-run-in baseline and once at 3mo follow-up visit
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Systane Complete PF (Treatment) | Tear Lipid Layer Thickness | 0.72 nm |
| Refresh Relieva PF (Control) | Tear Lipid Layer Thickness | -7.58 nm |
| Refresh Optive Mega-3 PF (Active Comparator 1) | Tear Lipid Layer Thickness | 2.06 nm |
| CVS Health Lubricant Eye Drop (PG 0.6%) (Active Comparator 2) | Tear Lipid Layer Thickness | 1.41 nm |
Secondary
Tear Film Thinning Rate
Change in Tear Film Thinning rate (3mo follow-up - post-run-in baseline)
Time frame: Tear Film Thinning Rate measured once at post-run-in baseline and once at 3mo follow-up visit
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Systane Complete PF (Treatment) | Tear Film Thinning Rate | 0.33 % Area of Fluorescein Darkening / sec |
| Refresh Relieva PF (Control) | Tear Film Thinning Rate | 1.71 % Area of Fluorescein Darkening / sec |
| Refresh Optive Mega-3 PF (Active Comparator 1) | Tear Film Thinning Rate | 0.02 % Area of Fluorescein Darkening / sec |
| CVS Health Lubricant Eye Drop (PG 0.6%) (Active Comparator 2) | Tear Film Thinning Rate | 0.70 % Area of Fluorescein Darkening / sec |
Secondary
Tear Lipid Layer Uniformity
Change (3mo follow-up - post-run-in baseline) in Tear Lipid Layer Thickness Coefficient of Variation (CV). The CV is calculated as the standard deviation divided by the mean lipid layer thickness. A greater value of the CV indicates more variability in lipid layer thickness, a smaller value of the CV indicates a more uniformly thick lipid layer.
Time frame: Lipid Layer Uniformity measured once at post-run-in baseline and once at 3mo follow-up visit
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Systane Complete PF (Treatment) | Tear Lipid Layer Uniformity | -0.15 Unitless |
| Refresh Relieva PF (Control) | Tear Lipid Layer Uniformity | -0.77 Unitless |
| Refresh Optive Mega-3 PF (Active Comparator 1) | Tear Lipid Layer Uniformity | -0.01 Unitless |
| CVS Health Lubricant Eye Drop (PG 0.6%) (Active Comparator 2) | Tear Lipid Layer Uniformity | -0.23 Unitless |
Other Pre-specified
Exploratory - Subjective Symptoms - DEQ-5
Change in 5-Item Dry Eye Questionnaire (DEQ-5) score (3mo follow-up - post-run-in baseline)
Time frame: DEQ-5 questionnaire administered once at post-run-in baseline and once at 3mo follow-up visit
Population: The DEQ-5 questionnaire was not administered to any subjects due to logistical issues.
Other Pre-specified
Exploratory - Subjective Symptoms - OSDI Questionnaire
Change (3mo follow-up - post-run-in baseline) in Ocular Surface Disease Index (OSDI) score. The OSDI questionnaire score ranges from 0-100, with higher scores indicating more severe symptoms of Dry Eye Disease.
Time frame: OSDI questionnaire administered once at post-run-in baseline and once at 3mo follow-up visit
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Systane Complete PF (Treatment) | Exploratory - Subjective Symptoms - OSDI Questionnaire | 2.88 units on a scale | Standard Deviation 13.45 |
| Refresh Relieva PF (Control) | Exploratory - Subjective Symptoms - OSDI Questionnaire | 4.90 units on a scale | Standard Deviation 16.31 |
| Refresh Optive Mega-3 PF (Active Comparator 1) | Exploratory - Subjective Symptoms - OSDI Questionnaire | 2.79 units on a scale | Standard Deviation 15.22 |
| CVS Health Lubricant Eye Drop (PG 0.6%) (Active Comparator 2) | Exploratory - Subjective Symptoms - OSDI Questionnaire | 1.30 units on a scale | Standard Deviation 9.48 |
Other Pre-specified
Exploratory - Subjective Symptoms - SANDE
Change in Symptom Assessment questionnaire iN Dry Eye (SANDE) score (3mo follow-up - post-run-in baseline)
Time frame: SANDE questionnaire administered once at post-run-in baseline and once at 3mo follow-up visit
Population: The SANDE questionnaire was not administered to any subjects due to logistical issues.